322 



DESCRIPTIONS OF ANTIBIOTICS 



fj.g per ml on Proteus and Xocardia aster jiies, some 

 atypical Fseadomonas and certain others, but 

 otherwise inactive on gram-negative bacteria. 

 Inactive on rickettsiae and viruses (9, 11). Slight 

 antiprotozoal activity (8). Inhibits Blastomyces 

 dermatitidis at 15 jug per ml (9), but not other 

 fungi (8). Gives rise to long filaments in gram- 

 negative but not gram-positive bacteria (18). 

 Mg^^ moderately reverses the activity of novo- 

 biocin against gram-negative but not gram-posi- 

 tive bacteria, as do Ca+"'", Sr++ and Ba++ to a lesser 

 extent (23). Bound and inactivated by serum (59). 

 Activity decreases with increasing pH (10). 

 Synergistic activity with many antibiotics (7). 

 Resistance develops rapidly (10). No cross-resist- 

 ance with common antilnotics. Occasionally, in- 

 crease of resistance to novobiocin is accompanied 

 by a decreasing resistance to other antibiotics (5, 

 6). Dihydronovobiocin has activity in vitro and 

 in vivo. Similar to novobiocin (25, 31). Active in 

 mice on Staph, aitreus. Streptococcus heniolyticus, 

 D. pneumoniae, Hemophilus, Pr. vulgaris, and 

 Pasteurella multocida (5, 6, 8). Conflicting reports 

 on activity in vivo on Sal. tijphosa and A', pneu- 

 moniae (6, 8). Some activity on downy mildew of 

 cucumber {Pseudoperonospora cubensis) has been 

 claimed (27). 



Toxicity: Novobiocin: LD;,ii (mice) 262 to 300 mg 

 per kg intraperitoneally (13) , about 400 mg per kg 

 (9) or 1 gm per kg orally (13) , and 407 to 424 mg per 

 kg intravenously. LD.=,o (guinea pigs) 11.5 mg per 

 kg intraperitoneally, and 27.8 mg per kg sub- 

 cutaneously. Moderately toxic to rabbit skeletal 

 muscle, dog liver and kidney at high doses; local 

 tissue injury on repeated subcutaneous injections 

 (13, 22). Side effects in human beings include rash, 

 leukopenia, and eosinophilia (20). Highest con- 

 centration permitting migration of epithelial 

 cells in tissue culture is 200 yug per ml (34). Dihy- 

 dronovobiocin: LDoo (mice) 325 mg per kg intra- 

 venously, and about 1100 mg per kg orally (22). 



Utilization: Effective in certain infections 

 caused by some gram-positive organisms, but 

 primarily useful in infections, especially staphy- 

 lococcal, caused by organisms resistant to other 

 antibiotics. Resistance to novobiocin develops 

 rapidly in clinical use. Recommended for use 

 concomitantly with other antibiotics (19). Not 

 effective in infections caused by enterococci or 

 actinomycetes (20). Possible use in certain Proteus 

 infections (17) and brucellosis (29). 



References: 



1. Waga, Y. J. Antibiotics (Japan) 6A: 



66-72, 1953. 



2. Kaczka, E. A. e/ n/. J. Am. Chem. Soc. 77: 



6404-6405, 1955. 



1955- 



1955- 



3. Hoeksema, H. et al. J. Am. Chem. Soc. 



77:6710-6711, 1955. 



4. Welch, H. and Wright, W. W. Antibiotics 



& Chemotherapy 5: 670-673, 1955. 



5. Martin, W. J. et al. Proc. Staff Meetings 



Mayo Clinic 30: 540-551, 1955. 



6. Lin, F. K. and Coriell, L. L. Antibiotics 



Ann. 1955-1956, pp. 634-639. 



7. Wallick, H. et al. Antibiotics Ann. 



1956, pp. 909-917. 



8. Frost, B. M. et al. Antibiotics Ann. 



1956, pp. 918-923. 



9. Verwey, W. F. et al. Antibiotics Ann. 



1955-1956, pp. 924-928. 



10. Finland, M. Antibiotics Ann. 1955-1956 



p. 929. 



11. Smith, C. G. et al. Antibiotics & Chemo- 



therapy 6: 135-142, 1956. 



12. Hoeksema, H. et al. Antibiotics & Chemo- 



therapy 6: 143-148, 1956. 



13. Larson, E. J. et al. Antibiotics & Chemo- 



therapy 6: 226-230, 1956. 



14. Hinman, J. W. et al. J. Am. Chem. Soc. 



78: 1072-1074, 1956. 



15. Shunk, C. H. et al. J. Am. Chem. Soc. 78: 



1770-1771, 1956. 



16. Walton, E. et al . J. Am. Chem. Soc. 78: 



5454-5455, 1956. 



17. Nichols, R. L. and Finland, M. Antibiotic 



Med. 2: 241-257, 1956. 



18. Brock, T. D. J. Bacteriol. 72: 320-323, 



1956. 



19. Kirby, W. M. M. et al. Arch. Internal Med. 



98: 1-7, 1956. 



20. Pearson, J. Z. et al. Arch. Internal Med. 



98: 273-283, 1956. 



21. Tanner, F. W. et al. Given in Beesch, S. C. 



and Shull, G. M. Ind. Eng. Chem. 48: 

 1585-1603. 1956. 



22. Rolland, G. et al. II. Farm. (Ed. Sci.) 11: 



549-561, 1956. 



23. Weinberg, E. 1). Antiliiotics Ann. 1056- 



1062, 1956-1957. 



24. Yegian, D. and Budd, V. Am. Rev. Tulierc. 



76: 272-278, 1957. 



25. Hinman, J. W. et al. J. Am. Chem. Soc. 



79: 3789-3800, 1957. 



26. Hinman, J. W. et al. J. Am. Chem. Soc. 



79: 5321-5322, 1957. 



27. Ark, P. A, and Thompson, J. B. Plant 



Disease Reptr. 41: 452-459. 1957. 



28. Chaiet, L. and Wolf, F. J. Antibiotics & 



Chemotherapy 7:231-234, 1957. 



29. Gost, J. T. Antibiotics Ann. 915-919, 



1957-1958. 



